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Antidepressants and Mood Stabilizers > Major depressive d/o > Flashcards

Major depressive d/o Flashcards

1
Q

What are antidepressants specifically prescribed for?

A
  • Major depressive disorder
  • Affective disorders that are characteristized by extreme depression (dysphoria), extreme elation (mania), or both.
  • Monopolar depression may affect 15% of all adults during any given year of their lifetime
  • Treatment usually takes 2-4 weeks and leads to 85% remission
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2
Q

Affective disorders

A
  • Depression
  • Result from a chemical imbalance between 3 NT
  • NE, serotonin and perhaps dopamine
  • Recent research has suggested that beta-adrenergic receptors may be involved
  • Beta blockers often give an antidepressant effect (pts get depressed when they come off of the beta blockers)
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3
Q

As a class of drugs, antidepressants are generally:

A
  • orally administered (IM admin very infrequent and limited to specific drugs)
  • very few injectable preparations. Most tx of depression is outpt, so PO is necessary
  • 90-95% bound to plasma proteins (DRUG INTERACTIONS. Will have more free drug than should. Only 5-10 percent remain free to produce an effect)
  • metabolized by the liver, with metabolites excreatd in urine
  • drugs with long “half-lives” (imiparamin-t1/2=24 hours)
  • drugs with a relatively small therapeutic index
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4
Q

5 prominent classes of antidepressant drugs:

A
  1. Tricyclics
    • tertiary amine tricyclics
    • secondary amine tricyclics
  2. Selective Serotonin Reuptake Inhibitors (SSRI)
  3. Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRI’s)
  4. Atypical
  5. Monomine Oxidase Inhibitors (MAOI’s )
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5
Q

Tricyclics

A
  • attempt to remedy depression by inactivating the “amine” pump on the presynaptic nerve terminal and thus limiting the reuptke of both NE and serotonin.
  • Unfortunately, many also have effects at muscarinic receptors, histamine type-1 receptors and alpha-1 receptors
  • 2 general types of tricyclics:
    • tertiary amine tricyclics
    • secondary amine tricyclics

Tertiary amine tricyclics:
bind to the serotonin transporter, which is the predominant binding affinity…
Serontonin is a very complex system, when there is an increase serotonin there is a decrease in appetite….increase in mood..decrease sex libido and function and increase sedation.
-modulatory NT..works with other neurotransmitters, which means that it works with glucomate..NA, etc..no autonomic s/e…
-if the drug interfers with libido or sexual s/e will cause non compliance..you need a good profile on these pt

Secondary Amine Tricyclics:
have affinity for serotonin and an added affinity for NE transporter…increase BP..decrease appetite..increase alertness…anti SLUDE effects

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6
Q

Name 5 tertiary amine tricyclics:

A
  1. Amitryptyline (Elavil)
  2. Clomipramine (Anafranil)
  3. Doxepin (Sinequan)
  4. imipramine (Tofranil)
  5. trimipramine (surmontil)
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7
Q

Amitryptyline (Elavil)

A
  • Tertiary amine tricyclics

- can be given IM

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8
Q

Clomipramine (Anafranil)

A
  • tertiary amine tricyclics

- usually given for obsessive-compulsive d/o (OCD); not very selective, can cause seizures

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9
Q

Doxepin (Sinequan)

A
  • tertiary amine tricyclic

- increased sedation, but absence of cardiovasculare s/e

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10
Q

imipramine (tofranil)

A
  • tertiary amine tricyclic

- can be given IM and a long-acting “pamoate” formulation is available

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11
Q

trimipramine (Surmontil)

A
  • tertiary amine tricyclic
  • very sedating and moderately anticholinergic
  • opposite SLUDE
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12
Q

Name 5 Secondary Amine Tricyclics

A
  • Amoxapine (Asendin)
  • Desipramine (Norpram)
  • Maprotiline (Ludiomil)
  • Nortryptyline (Pamelor)
  • Protryptyline (Vivactil)
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13
Q

Amoxapine (Asendin)

A

secondary amine tricyclics

a dibenzodiazepine that is a metabolite of the antipsychotic loxapin; therefore, it has a dopaminergic as well as adrenergic mechanism

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14
Q

desipramine (Norpram)

A

-secondary amine tricyclics

naturally occurring metabolite of imipramine

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15
Q

maprotiline (ludiomil)

A

secondary amine tricyclics

very new with increased potential for seizures

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16
Q

nortryptyline (pamelor)

A

secondary amine tricyclics

metabolite of amitryptyline; indicated for elderly patients

17
Q

protryptyline (Vivactil)

A

secondary amine tricyclics

lacks sedative properites; often prescribed for “sleepy” depressives

18
Q

Selective Serotonin Reuptake Inhibitors (SSRI’s)

A

often first choice for monopolar depression and they appear to be the most effective agents in the treatment of premenstrual dysphoric disorder (PMDD)

  1. citalopram (Celexa)
  2. escitalopram (Lexapro)
  3. fluoxetine (Prozac), t1/2=72 hours
  4. fluvoxamine (Luvox)
  5. paroxetine (Paxil)
  6. sertraline (Zoloft), t1/2=36 hours
19
Q

escitalopram (Lexapro)

A

SSRI

also approved for adolescents

20
Q

Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRI’s):

A

these have fewer antimuscarinic and antihistaminic effects than the tricyclics and have more of an adrenergic effect compared to SSRIs

  1. duloxetine (Cymbalta)
  2. milnacipran (Ixel)
  3. venlafaxine (Effexor)
  4. desvenlafaxine (Pritiq)
21
Q

paroxetine (Paxil)

A

SSRI

noted for its anticholinergc s/e; recently approved for social phobia

22
Q

duloxetine (Cymbalta)

A
  • SNRI has 1:10 affinity for 5-HT and NE transporter, respectively.
  • It is also one of two SNRI’s FDS approved for fibromyalgia
  • Doctors may prescribe serotonin and norepinephrine reuptake inhibitors (SNRIs) when mood problems are a major symptom of fibromyalgia. SNRIs are also used for people without fibromyalgia who have depression.
  • Some people with fibromyalgia who take SNRIs notice an improvement in a number of symptoms, including depression, pain, and fatigue
23
Q

milnacipran (Ixel)

A
  • SNRI has a 1:1 affinity for 5-HT and NE transporters.

- It is the second SNRI that is FDA-approved for the tx of fibromyalgia

24
Q

venlafaxine (Effexor)

A
  • a phenethylamine that has been shown to produce withdrawal following chronic tx and rebound effects
  • this SNRI has 1:30 affinity for the 5-HT and NE transporters
25
Q

desvenlafaxine (Pritiq)

A

SNRI

an isomer of venlafaxine with similar pharmacological properties to those of the parent compound

26
Q

Name 6 atypical major depressive d/o drugs:

A
  1. bupropion (Wellbutrin or Zyban)
  2. nefazodone (Serzone)
  3. mirtazapine (Remeron)
  4. reboxetine (Edronax)
  5. trazadone (Desyrel)
  6. vilazodone (Viibryd)
27
Q

bupropion (Wellbutrin or Zyban)

A

atypical

known for its ability to block the reuptake of dopamine, as well as norepinephrin

3-fold increase in the incidence of seizures

28
Q

nefazodone (Serzone)

A

atypical

prominent effects are through serotonergic mechanisms

this drug also has a block box warning on the labeling advising pts that are rare, but life-threatening

liver failure can occur

29
Q

mirtazapine (Remeron)

A

SEDATION is one of its most prominent adverse effects possible due to its capacity for blocking histamine receptors

this drug also has the capacity to block 5-HT2A receptors, alpha-1 receptors, and alpha 2 autoreceptors CENTRALLY

30
Q

reboxetine (Edronax)

A

atypical

selectively inhibits NE uptake (NRI)

31
Q

trazadone (Desyrel)

A

atypical

50mg of this drug is widely prescribed by psychiatrists as a sedative hypnotic for those with difficulty sleeping

Advantages include the virtual absence of cardiac and anticholinergic s/e owing to its prominent serotonergic properties

priapism has been reported

32
Q

vilazodone (Viibryd)

A

atypical

new (approved in 2011) “dual action” antidepressant

can both block the serotonin reuptake transporter and act as a partial agonist at the 5-HT!A receptor

Seems to be well tolerated and may produce a low incidence of sexual side effects

33
Q

Monoamine Oxidase Inhibitors (MAOI’s)

A

are usually used only to tx refactory depression

attempt to remedy this by inactivating the enzyme (MAO) that metabolizes norephinephrine and serotonin

isocarboxazid (Marplan)
phenelzine (Nardil)
tranylcypromine (Parnate)

34
Q

Antidepressant A/E:

A

SEDATION is the largest initial problem

  • CARDIOVASCULAR EFFECTS are some of the most serious s/e.
    • orthostatic hypotension can lead to tachycardia
    • antimuscarinic effects at the SA node can unmask sympathetic influences
  • SEIZURES- many antidepressants lower seizure threshold
  • SEXUAL DYSFUNCTION- a very troubling a/e for pts…this can lead to non-compliance
  • BLOOD ABNORMALITIES- agranulocytosis is rare, these drgs can cause bone marrow depression, thrombocytopenia or eosinophilia
    • elderly people may be at greater risk for hyponatremia.
      - symptoms may include HA, weakness or felling unsteady; confusion, problems concentrating or thinking or memory problems

SEROTONIN SYNDROME- agitation, hallucinations, coma or other changes in mental status; coordination problems or muscle twitching; fast heartbeat, high or low BP; sweating or fever; nausea, vomiting or diarrhea; muscle stiffness or tightness

ABNORMAL BLEEDING- antidepressant medicines may increase your risk of bleeding or bruising, esp if you take the blood thinner warfarin (Coumadin, Jantoven), a non-steroidal anti-inflammatory drug (NSAID), or aspirin

MANIC EPISODES- greatly increased energy; severe trouble sleeping; racing thoughts; reckless behavior; unusually grand ideas; excessive happiness or irritability; talking more or faster than usual

SUICIDALITY- antidepressants increased the rrisk of suicidal thinking and behavior in children, teens, and young adults compared to placebo.

  • depression and certain other psychiatric d/o are themselves associated with increases in the risk of suicide.
  • Patients of all ages who are started on antidepressant tx should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior
35
Q

Antidepressant drug interactions:

A

-should not be given with other CNS depressants, any antimuscarinic agents, or a MAOI

  • indirect-actin sympathomimetics:
    • amphetamine
    • tyramine
    • potential for local anesthetic solutions with epi to cause HTN crisis with pts taking TCAs and MAOIs
  • mixed-acting sympathomimetics (OTC):
    • pseudoephedrine
  • Tamoxifen and SSRIs: SSRIs are commonly used to tx depression in breast CA. Frequently they are also taking tamoxifen subsequent to remission to prevent the recurrence and to decrease hot flashes.
    • this prodrug is metabolized by CYP2D6 and the SSRIs fluoxetine, paroxetine, and sertraline inhibit CYP2D6.
    • this interaction increases recurrence rate of breast CA…you could be facilitating breast CA occurrence
    • ok to use citalopram and escitalopram b/c these SSRis are only weak inhibitors of CYP2D6

The TCAs can also function as a local anesthetic and cause an interaction b/w local anesthetics….you can block the effects of the LA when using in conjunction with a TCA…not a huge interaction..just be aware

Antidepressants and Mood Stabilizers (2 decks)

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